Optimal Percutaneous Treatment Approach to Unprotected Ostial Left Anterior Descending Artery Disease: A Meta-Analysis and Systematic Review.

BACKGROUND: The optimal management strategy for significant unprotected ostial left anterior descending artery (LAD) disease remains undefined. Merits of the two most common percutaneous approaches are considered in this quantitative synthesis. METHOD: A meta-analysis was performed to compare ostial stenting (OS) and crossover stenting (CS) in the treatment of unprotected ostial LAD stenosis. The primary outcome is the disparity in target lesion revascularisation (TLR). The Mantel-Haenszel method was employed with random effect model, chosen a priori to account for heterogeneity among the included studies. RESULTS: Seven studies comprising 1,181 patients were included in the analyses. Of these, 482 (40.8%) patients underwent CS. Overall, there was a statistically significant trend in favour of CS (odds ratio 0.51, 95% confidence interval 0.30-0.86, p=0.01) with respect to the rate of TLR at follow-up. This remained true when TLR involving the left circumflex artery (LCx) was considered, even when there was a greater need for unintended intervention to the LCx during the index procedure (odds ratio 6.68, 95% confidence interval: 1.69-26.49, p=0.007). Final kissing balloon inflation may reduce the need for acute LCx intervention. Imaging guidance appeared to improve clinical outcomes irrespective of approach chosen. CONCLUSIONS: In the percutaneous management of unprotected ostial LAD disease, CS into the left main coronary artery (LMCA) appeared to reduce future TLR. Integration of intracoronary imaging was pivotal to procedural success. The higher incidence of unintended LCx intervention in the CS arm may be mitigated by routine final kissing balloon inflation, although the long-term implication of this remains unclear. In the absence of randomised trials, clinicians' discretion remains critical.

Fractional Flow Reserve and Angiography Guided Complete Revascularization in Primary Percutaneous Coronary Intervention: A Systematic Review and Network Meta-Analysis.

Using a network meta-analysis, this study compared fractional flow reserve (FFR) guided with angiography-guided revascularization of non-culprit lesions in ST elevation myocardial infarction (STEMI). We also assessed if early complete revascularization is superior to delayed revascularization. We conducted a network meta-analysis using Net Meta XL of trials of STEMI patients with multivessel disease and compared revascularization strategies. The primary outcomes of interest were rate of revascularization, myocardial infarction, and all-cause mortality. Ten studies were included in our analysis comprising 7981 patients with 4484 patients undergoing complete revascularization and 3497 patients with culprit-only revascularization. There was no significant reduction in all-cause death, myocardial infarction, or revascularization using FFR guidance. There was significant reduction in repeat revascularization with complete revascularization irrespective of timing of percutaneous coronary intervention (PCI) compared with the culprit-only group. There was an overall trend favoring earlier revascularization. For patients with multivessel disease presenting with ST-elevation MI, complete revascularization significantly reduces repeat revascularization compared with culprit-only treatment. FFR guidance is non-superior to angiography-guided revascularization. Furthermore, there was significant reduction in repeat revascularization irrespective of timing of PCI to non-culprit vessels.

Safety, Feasibility and Economic Analysis of Same Day Discharge Following Elective Percutaneous Coronary Intervention.

Background: Advances in percutaneous coronary intervention (PCI) has made the possibility of facilitating same day discharge (SDD) of patients undergoing intervention. We sought to investigate the feasibility, safety and economic impact of such a service. Methods: We retrospectively collected data on all patients undergoing outpatient PCI at our institution over a 12-month period. We included in-hospital and 30-day major adverse cardiac events (MACE), vascular complications, acute kidney injury and any re-hospitalisations. We analysed the cost effectiveness of SDD compared to overnight admission post PCI and staged PCI following diagnostic angiography. Results: A total of 147 patients undergoing PCI with 129 patients deemed suitable for SDD (88%). Mean age was 65.7 years. Most patients had type C lesions (60.3%); including 4 chronic total occlusions (CTOs). At 30-day follow-up there were no MACE events (0%). There were 10 (7.8%) re-hospitalisations of which majority (70%) were non cardiac presentations. We also included cost analysis for an elective PCI with SDD, which equated to $2090 per patient (total of $269 610 for cohort). Elective PCI with an overnight admission was $4440 per patient (total of $572 760 for cohort), an additional $2350 per patient (total $303 150). Total cost of an angiogram followed by a staged PCI with an overnight stay was $4700 per patient (total $606 300). Conclusion: SDD is safe and feasible in the majority of patients that have elective coronary angiography that require PCI. SDD leads to a significant reduction in total cost and hospital stay of patients undergoing elective PCI.

Impact of coronary artery disease on contractile function and ventricular-arterial coupling during exercise: Simultaneous assessment of left-ventricular pressure-volume and coronary pressure and flow during cardiac catheterization.

Coronary artery disease (CAD) can adversely affect left ventricular (LV) performance during exercise by impairment of contractile function in the presence of increasing afterload. By performing invasive measures of LV pressure-volume and coronary pressure and flow during exercise, we sought to accurately measure this with comparison to the control group. Sixteen patients, with CCS class >II angina and CAD underwent invasive simultaneous measurement of left ventricular pressure-volume and coronary pressure and flow velocity during cardiac catheterization. Measurements performed at rest were compared with peak exercise using bicycle ergometry. The LV contractile function was measured invasively using the end-systolic pressure-volume relationship, a load independent marker of contractile function (Ees). Vascular afterload forces were derived from the ratio of LV end-systolic pressure to stroke volume to generate arterial elastance (Ea). These were combined to assess cardiovascular performance (ventricular-arterial [VA] coupling ratio [Ea/Ees]). Eleven patients demonstrated flow-limiting (FL) CAD (hyperemic Pd/Pa <0.80; ST-segment depression on exercise); five patients without flow-limiting (NFL) CAD served as the control group. Exercise in the presence of FL CAD was associated impairment of Ees, increased Ea, and deterioration of VA coupling. In the control cohort, exercise was associated with increased Ees and improved VA coupling. The backward compression wave energy directly correlated with the magnitude contraction as measured by dP/dTmax (r = 0.88, p = 0.004). This study demonstrates that in the presence of flow-limiting CAD, exercise to maximal effort can lead to impairment of LV contractile function and a deterioration in VA coupling compared to a control cohort.

Physiological Impact of Afterload Reduction on Cardiac Mechanics and Coronary Hemodynamics Following Isosorbide Dinitrate Administration in Ischemic Heart Disease.

Understanding the cardiac-coronary interaction is fundamental to developing treatment strategies for ischemic heart disease. We sought to examine the impact of afterload reduction following isosorbide dinitrate (ISDN) administration on LV properties and coronary hemodynamics to further our understanding of the cardiac-coronary interaction. Novel methodology enabled real-time simultaneous acquisition and analysis of coronary and LV hemodynamics in vivo using coronary pressure-flow wires (used to derive coronary wave energies) and LV pressure-volume loop assessment. ISDN administration resulted in afterload reduction, reduced myocardial demand, and increased mechanical efficiency (all P<0.01). Correlations were demonstrated between the forward compression wave (FCW) and arterial elastance (r=0.6) following ISDN. In the presence of minimal microvascular resistance, coronary blood flow velocity exhibited an inverse relationship with LV elastance. In summary this study demonstrated a reduction in myocardial demand with ISDN, an inverse relationship between coronary blood flow velocity and LV contraction-relaxation and a direct correlation between FCW and arterial elastance. The pressure volume-loop and corresponding parameters b The pressure volume loop before (solid line) and after (broken line) Isosorbide dintrate.

Internet search volume for chest pain during the COVID-19 pandemic.

During the COVID-19 pandemic there has been a reduction in hospital admissions for acute myocardial infarction. This manuscript presents the analysis of Google Trends meta-data and shows a marked spike in search volume for chest pain that is strongly correlated with COVID-19 case numbers in the United States. This raises a concern that fear of contracting COVID-19 may be leading patients to self-triage using internet searches.

Colchicine in Patients With Acute Coronary Syndrome: The Australian COPS Randomized Clinical Trial.

BACKGROUND: Inflammation plays a crucial role in clinical manifestations and complications of acute coronary syndromes (ACS). Colchicine, a commonly used treatment for gout, has recently emerged as a novel therapeutic option in cardiovascular medicine owing to its anti-inflammatory properties. We sought to determine the potential usefulness of colchicine treatment in patients with ACS. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled trial involving 17 hospitals in Australia that provide acute cardiac care service. Eligible participants were adults (18-85 years) who presented with ACS and had evidence of coronary artery disease on coronary angiography managed with either percutaneous coronary intervention or medical therapy. Patients were assigned to receive either colchicine (0.5 mg twice daily for the first month, then 0.5 mg daily for 11 months) or placebo, in addition to standard secondary prevention pharmacotherapy, and were followed up for a minimum of 12 months. The primary outcome was a composite of all-cause mortality, ACS, ischemia-driven (unplanned) urgent revascularization, and noncardioembolic ischemic stroke in a time to event analysis. RESULTS: A total of 795 patients were recruited between December 2015 and September 2018 (mean age, 59.8±10.3 years; 21% female), with 396 assigned to the colchicine group and 399 to the placebo group. Over the 12-month follow-up, there were 24 events in the colchicine group compared with 38 events in the placebo group (P=0.09, log-rank). There was a higher rate of total death (8 versus 1; P=0.017, log-rank) and, in particular, noncardiovascular death in the colchicine group (5 versus 0; P=0.024, log-rank). The rates of reported adverse effects were not different (colchicine 23.0% versus placebo 24.3%), and they were predominantly gastrointestinal symptoms (colchicine, 23.0% versus placebo, 20.8%). CONCLUSIONS: The addition of colchicine to standard medical therapy did not significantly affect cardiovascular outcomes at 12 months in patients with ACS and was associated with a higher rate of mortality. Registration: URL: https://www.anzctr.org.au; Unique identifier: ACTRN12615000861550.

Resting Coronary Flow Varies With Normal Cardiac Catheter Laboratory Stimuli.

BACKGROUND: Growing evidence supports physiology-guided revascularization, with Fractional Flow Reserve (FFR) the most commonly used invasive measure of coronary blood flow impairment at the time of diagnostic angiography. Recently, there has been growing interest in stenosis severity indices measured at rest, such as Instantaneous Wave Free Ratio (iFR) and the ratio of distal coronary to aortic pressure at rest (resting Pd/Pa). Their reliability may, theoretically, be more susceptible to changes in microvascular tone and coronary flow. This study aimed to assess variability of resting coronary flow with normal catheter laboratory stimuli. METHODS: Simultaneous intracoronary pressure (Pd) and Doppler Average Peak Flow Velocity (APV) recordings were made at rest and following the verbal warning preceding an intravenous adenosine infusion. RESULTS: 72 patients undergoing elective angiography were recruited (mean age 62 years, 52.7% male) with a wide range of coronary artery disease severity (FFR 0.86 ±â€¯0.09). Average peak flow velocity varied significantly between measurements at rest and just prior to commencement of adenosine, with a mean variation of 10.2% (17.82 ±â€¯9.41 cm/s vs. 19.63 ±â€¯10.44 cm/s, p < 0.001) with an accompanying significant drop in microvascular resistance (6.27 ±â€¯2.73 mm Hg·cm-1·s-1 vs. 5.8 ±â€¯2.92 mm Hg·cm-1·s-1, p < 0.001). These changes occurred without significant change in systemic hemodynamic measures. Whilst there was a trend for an associated change in the resting indices, Pd/Pa and iFR, this was statistically and clinically not significant (0.92 ±â€¯0.08 vs. 0.92 ±â€¯0.08, p = 0.110; and 0.90 ±â€¯0.11 vs. 0.89 ±â€¯0.12, p = 0.073). CONCLUSION: Resting coronary flow and microvascular resistance vary significantly with normal catheter laboratory stimuli, such as simple warnings. The clinical impact of these observed changes on indices of stenosis severity, particularly those measured at rest, needs further assessment within larger cohorts.

Doppler Versus Thermodilution-Derived Coronary Microvascular Resistance to Predict Coronary Microvascular Dysfunction in Patients With Acute Myocardial Infarction or Stable Angina Pectoris.

Coronary microvascular resistance is increasingly measured as a predictor of clinical outcomes, but there is no accepted gold-standard measurement. We compared the diagnostic accuracy of 2 invasive indices of microvascular resistance, Doppler-derived hyperemic microvascular resistance (hMR) and thermodilution-derived index of microcirculatory resistance (IMR), at predicting microvascular dysfunction. A total of 54 patients (61 ± 10 years) who underwent cardiac catheterization for stable coronary artery disease (n = 10) or acute myocardial infarction (n = 44) had simultaneous intracoronary pressure, Doppler flow velocity and thermodilution flow data acquired from 74 unobstructed vessels, at rest and during hyperemia. Three independent measurements of microvascular function were assessed, using predefined dichotomous thresholds: (1) coronary flow reserve (CFR), the average value of Doppler- and thermodilution-derived CFR; (2) cardiovascular magnetic resonance (CMR) derived myocardial perfusion reserve index; and (3) CMR-derived microvascular obstruction. hMR correlated with IMR (rho = 0.41, p <0.0001). hMR had better diagnostic accuracy than IMR to predict CFR (area under curve [AUC] 0.82 vs 0.58, p <0.001, sensitivity and specificity 77% and 77% vs 51% and 71%) and myocardial perfusion reserve index (AUC 0.85 vs 0.72, p = 0.19, sensitivity and specificity 82% and 80% vs 64% and 75%). In patients with acute myocardial infarction, the AUCs of hMR and IMR at predicting extensive microvascular obstruction were 0.83 and 0.72, respectively (p = 0.22, sensitivity and specificity 78% and 74% vs 44% and 91%). We conclude that these 2 invasive indices of coronary microvascular resistance only correlate modestly and so cannot be considered equivalent. In our study, the correlation between independent invasive and noninvasive measurements of microvascular function was better with hMR than with IMR.

Deleterious Effects of Cold Air Inhalation on Coronary Physiological Indices in Patients With Obstructive Coronary Artery Disease.

Background Cold air inhalation during exercise increases cardiac mortality, but the pathophysiology is unclear. During cold and exercise, dual-sensor intracoronary wires measured coronary microvascular resistance ( MVR ) and blood flow velocity ( CBF ), and cardiac magnetic resonance measured subendocardial perfusion. Methods and Results Forty-two patients (62±9 years) undergoing cardiac catheterization, 32 with obstructive coronary stenoses and 10 without, performed either (1) 5 minutes of cold air inhalation (5°F) or (2) two 5-minute supine-cycling periods: 1 at room temperature and 1 during cold air inhalation (5°F) (randomized order). We compared rest and peak stress MVR , CBF , and subendocardial perfusion measurements. In patients with unobstructed coronary arteries (n=10), cold air inhalation at rest decreased MVR by 6% ( P=0.41), increasing CBF by 20% ( P<0.01). However, in patients with obstructive stenoses (n=10), cold air inhalation at rest increased MVR by 17% ( P<0.01), reducing CBF by 3% ( P=0.85). Consequently, in patients with obstructive stenoses undergoing the cardiac magnetic resonance protocol (n=10), cold air inhalation reduced subendocardial perfusion ( P<0.05). Only patients with obstructive stenoses performed this protocol (n=12). Cycling at room temperature decreased MVR by 29% ( P<0.001) and increased CBF by 61% ( P<0.001). However, cold air inhalation during cycling blunted these adaptations in MVR ( P=0.12) and CBF ( P<0.05), an effect attributable to defective early diastolic CBF acceleration ( P<0.05) and associated with greater ST -segment depression ( P<0.05). Conclusions In patients with obstructive coronary stenoses, cold air inhalation causes deleterious changes in MVR and CBF . These diminish or abolish the normal adaptations during exertion that ordinarily match myocardial blood supply to demand.

Increasing proportion of ST elevation myocardial infarction patients with coronary atherosclerosis poorly explained by standard modifiable risk factors.

Aims Identification and management of the Standard Modifiable Cardiovascular Risk Factors (SMuRFs; hypercholesterolaemia, hypertension, diabetes and smoking) has substantially improved cardiovascular disease outcomes. However, cardiovascular disease remains the leading cause of death worldwide. Suspecting an evolving pattern of risk factor profiles in the ST elevation myocardial infarction (STEMI) population with the improvements in primary care, we hypothesized that the proportion of 'SMuRFless' STEMI patients may have increased. Methods/results We performed a single centre retrospective study of consecutive STEMI patients presenting from January 2006 to December 2014. Over the study period 132/695 (25%) STEMI patients had 0 SMuRFs, a proportion that did not significantly change with age, gender or family history. The proportion of STEMI patients who were SMuRFless in 2006 was 11%, which increased to 27% by 2014 (odds ratio 1.12 per year, 95% confidence interval: 1.04-1.22). The proportion of patients with hypercholesterolaemia decreased (odds ratio 0.92, 95% confidence interval 0.86-0.98), as did the proportion of current smokers (odds ratio 0.93, 95% confidence interval 0.86-0.99), with no significant change in the proportion of patients with diabetes and hypertension. SMuRF status was not associated with extent of coronary disease; in-hospital outcomes, or discharge prescribing patterns. Conclusion The proportion of STEMI patients with STEMI poorly explained by SMuRFs is high, and is significantly increasing. This highlights the need for bold approaches to discover new mechanisms and markers for early identification of these patients, as well as to understand the outcomes and develop new targeted therapies.

Physiology of Angina and Its Alleviation With Nitroglycerin: Insights From Invasive Catheter Laboratory Measurements During Exercise.

BACKGROUND: The mechanisms governing exercise-induced angina and its alleviation by the most commonly used antianginal drug, nitroglycerin, are incompletely understood. The purpose of this study was to develop a method by which the effects of antianginal drugs could be evaluated invasively during physiological exercise to gain further understanding of the clinical impact of angina and nitroglycerin. METHODS: Forty patients (mean age, 65.2±7.6 years) with exertional angina and coronary artery disease underwent cardiac catheterization via radial access and performed incremental exercise using a supine cycle ergometer. As they developed limiting angina, sublingual nitroglycerin was administered to half the patients, and all patients continued to exercise for 2 minutes at the same workload. Throughout exercise, distal coronary pressure and flow velocity and central aortic pressure were recorded with sensor wires. RESULTS: Patients continued to exercise after nitroglycerin administration with less ST-segment depression (P=0.003) and therefore myocardial ischemia. Significant reductions in afterload (aortic pressure, P=0.030) and myocardial oxygen demand were seen (tension-time index, P=0.024; rate-pressure product, P=0.046), as well as an increase in myocardial oxygen supply (Buckberg index, P=0.017). Exercise reduced peripheral arterial wave reflection (P<0.05), which was not further augmented by the administration of nitroglycerin (P=0.648). The observed increases in coronary pressure gradient, stenosis resistance, and flow velocity did not reach statistical significance; however, the diastolic velocity-pressure gradient relation was consistent with a significant increase in relative stenosis severity (k coefficient, P<0.0001), in keeping with exercise-induced vasoconstriction of stenosed epicardial segments and dilatation of normal segments, with trends toward reversal with nitroglycerin. CONCLUSIONS: The catheterization laboratory protocol provides a model to study myocardial ischemia and the actions of novel and established antianginal drugs. Administration of nitroglycerin causes changes in the systemic and coronary circulation that combine to reduce myocardial oxygen demand and to increase supply, thereby attenuating exercise-induced ischemia. Designing antianginal therapies that exploit these mechanisms may provide new therapeutic strategies.

Cardiac Arrest in Acute Myocardial Infarction: Concept of Circulatory Support With Mechanical Chest Compression and Impella to Facilitate Percutaneous Coronary Intervention.

Cardiogenic shock in the context of acute ST-elevation myocardial infarction (STEMI) remains a challenge to manage and results in significant mortality and morbidity, cardiac arrest in this setting even more so. The increase in myocardial oxygen demand and consumption with the use of inotropes is recognised as increasing mortality. Alternatives include the intra-aortic balloon pump (IABP), which has yet to be shown to improve outcomes, and extracorporeal membrane oxygenation (ECMO), which requires super-specialised techniques not widely available. We report a case of Anterior STEMI from a left main stem occlusion suffering with cardiac arrest on reaching the catheter laboratory table necessitating external mechanical compression with an Autopulse™. The patient remained in pulseless electrical activity (PEA) throughout, and was Autopulse dependent despite successful percutaneous coronary intervention (PCI). An Impella® was inserted for additional mechanical support and facilitated successful weaning from cardiopulmonary resuscitation (CPR). Despite 105minutes without a spontaneous output, we describe the first documented case of simultaneous use of Impella with mechanical CPR with a successful outcome; demonstrating a potential technique of good mechanical haemodynamic support to aide early revascularisation that may have potential utility in the treatment of cardiogenic shock and arrest.

Accurate and Standardized Coronary Wave Intensity Analysis.

OBJECTIVE: Coronary wave intensity analysis (cWIA) has increasingly been applied in the clinical research setting to distinguish between the proximal and distal mechanical influences on coronary blood flow. Recently, a cWIA-derived clinical index demonstrated prognostic value in predicting functional recovery postmyocardial infarction. Nevertheless, the known operator dependence of the cWIA metrics currently hampers its routine application in clinical practice. Specifically, it was recently demonstrated that the cWIA metrics are highly dependent on the chosen Savitzky-Golay filter parameters used to smooth the acquired traces. Therefore, a novel method to make cWIA standardized and automatic was proposed and evaluated in vivo. METHODS: The novel approach combines an adaptive Savitzky-Golay filter with high-order central finite differencing after ensemble-averaging the acquired waveforms. Its accuracy was assessed using in vivo human data. The proposed approach was then modified to automatically perform beat wise cWIA. Finally, the feasibility (accuracy and robustness) of the method was evaluated. RESULTS: The automatic cWIA algorithm provided satisfactory accuracy under a wide range of noise scenarios (≤10% and ≤20% error in the estimation of wave areas and peaks, respectively). These results were confirmed when beat-by-beat cWIA was performed. CONCLUSION: An accurate, standardized, and automated cWIA was developed. Moreover, the feasibility of beat wise cWIA was demonstrated for the first time. SIGNIFICANCE: The proposed algorithm provides practitioners with a standardized technique that could broaden the application of cWIA in the clinical practice as enabling multicenter trials. Furthermore, the demonstrated potential of beatwise cWIA opens the possibility investigating the coronary physiology in real time.

Contemporary Management of ST-Elevation Myocardial Infarction.

Recent advances have caused a major shift in the way ST-elevation myocardial infarctions are managed. This review explores the pharmacological and interventional techniques that have evidence for improving outcomes and the landmark trials that have sparked change. The new P2Y12 inhibitors, ticagrelor and prasugrel, have been shown to be superior to clopidogrel in STEMI patients undergoing primary percutaneous coronary intervention. Concurrently, many technical aspects of percutaneous coronary intervention have been further clarified by trial data, with bare-metal stents, routine thrombus aspiration and femoral access showing evidence of inferiority. Ongoing trials will provide more information on the role of non-culprit lesion PCI, bioresorbable vascular scaffolds, mechanical devices in persistent ischaemia and early automatic implantable cardioverter-defibrillators for inducible ventricular tachycardia.